Dengue virus (DENV), a mosquito-borne flavivirus, causes dengue fever, a potentially severe illness. Globally prevalent, it affects millions annually. DENV's life cycle involves replication in both mosquito vectors and human hosts. NS1, a nonstructural protein, is essential for viral replication and pathogenesis. Secreted NS1 interacts with host cells, influencing immune responses and contributing to vascular leakage, a hallmark of severe dengue.
NS1 exists as a monomer in infected cells, then forms a stable dimer upon secretion. The dimer can further associate into a hexameric lipoprotein particle on the cell surface or in circulation. NS1 is glycosylated in both the endoplasmic reticulum (ER) and the trans-Golgi network, stabilizing the hexamer and facilitating its secretion. Expressed early in infection, NS1 is found in the ER, the cell membrane, and secreted into the extracellular environment, predominantly as a soluble hexamer. This secretion allows NS1 to interact with various host cells and components, playing diverse roles in pathogenesis.
NS1 is crucial for efficient DENV replication. Intracellularly, it forms part of the viral replication complex, acting as a scaffolding protein to anchor the replication complex to the ER membrane. NS1 interacts with cellular proteins involved in lipid metabolism, which is essential for the formation of replication vesicles. Furthermore, NS1 impacts host cell signaling pathways, enhancing conditions conducive to viral replication. It also plays a role in evading host antiviral responses, thereby facilitating viral proliferation.
Fig. 1 NS1 in the DENV life cycle.1, 3
Soluble NS1 can disrupt tight junctions and the endothelial glycocalyx, increasing vascular permeability and leading to plasma leakage, a hallmark of severe dengue hemorrhagic fever. NS1 can trigger the activation of inflammasomes in macrophages, leading to inflammation and tissue damage. It can also induce inflammatory cytokine storms, contributing to systemic inflammation. NS1 interacts with toll-like receptors on immune cells, modulating immune responses and potentially contributing to immune evasion. Additionally, it may directly damage organs such as the liver and kidneys.
Antibodies targeting NS1 are critical for both diagnosis and potential therapy. NS1 is highly abundant during infection, making it a valuable diagnostic marker. Many murine- or human-derived anti-NS1 monoclonal antibodies (mAbs) have been developed, which can neutralize the protein's pathogenic effects, offering therapeutic potential. Anti-NS1 antibodies offer multiple therapeutic mechanisms, by not only limiting viral spread from infected cells during the early viremic phase but also mitigating NS1-driven disease progression in the critical phase. Furthermore, since NS1 is not a structural protein of the virus, anti-NS1 antibodies do not trigger antibody-dependent enhancement (ADE). Some mAbs targeting NS1 have shown promise in preclinical studies by reducing vascular leakage and viral load. Furthermore, NS1 is a target for vaccine development, with efforts focusing on inducing protective antibody responses.
Fig. 2 The possible pathogenic roles of DENV NS1 and antibody against NS1 as a therapeutic drug for dengue disease.2, 3
Leveraging rich experience in antibody research, Creative Biolabs provides highly specific and sensitive anti-DENV NS1 neutralizing antibodies, engineered to advance and optimize your diverse research objectives.
Recombinant Anti-DENV NS1 Antibody (V3S-0622-YC3214) (CAT#: V3S-0622-YC3214)
Target: DENV NS1
Host Species: Human
Target Species: Dengue Virus (DENV),
Application: ELISA,
Recombinant Anti-DENV NS1 Antibody (V3S-0622-YC3216) (CAT#: V3S-0622-YC3216)
Target: DENV NS1
Host Species: Human
Target Species: Dengue Virus (DENV),
Application: ELISA,
Recombinant Anti-DENV NS1 Antibody (V3S-0522-YC7315) (CAT#: V3S-0522-YC7315)
Target: DENV NS1
Host Species: Human
Target Species: Dengue Virus (DENV),
Application: WB,ELISA,IF,FuncS,
Recombinant Anti-DENV NS1 Antibody (V3S-1022-YC290) (CAT#: V3S-1022-YC290)
Target: DENV NS1
Host Species: Mouse
Target Species: Dengue virus (DENV),
Application: WB,
DENV NS1 (aa 178-273) Specific Recomb™ Antibody (V3S-1123-CJ5), Human IgG1 (CAT#: V3S-1123-CJ5)
Target: DENV NS1
Host Species: Human
Target Species: Dengue virus (DENV),
Application: WB,ELISA,FC,